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PubMed1991

The effect of preincubation with cimetidine on the N-hydroxylation of dapsone by human liver microsomes.

We have examined the ability of cimetidine to inhibit the oxidative metabolism and hence haemotoxicity of dapsone in vitro, using a two compartment system in which two Teflon chambers are separated by a semi-permeable membrane. Compartment A contained a drug metabolizing system (microsomes prepared from human or rat liver +/- NADPH), whilst compartment B contained human red cells. Preincubation (30 min) of human liver microsomes with cimetidine (0-1000 microM) and NADPH prior to the addition of dapsone (100 microM) and NADPH (1 mM) resulted in a concentration-dependent decrease in the concentrations of dapsone hydroxylamine (from 179 +/- 47 to 40 +/- 6 ng) in compartment B. This reduction of hydroxylamine metabolite was reflected in the concentration-dependent reduction in methaemoglobin measured (from 7.1 +/- 0.7 to 3.5 +/- 1.5%) in parallel experiments. Preincubation of microsomes with cimetidine in the absence of NADPH had no effect. The effect of cimetidine pretreatment on dapsone-dependent methaemoglobin was confirmed using microsomes prepared from a further three sources of human liver, as well as from rat liver.

Adolescent↗
PubMed1995

Dapsone for refractory chronic idiopathic thrombocytopenic purpura.

Fifteen patients with refractory chronic idiopathic thrombocytopenic purpura (ITP) were treated with dapsone (100 mg/d) for 1-31 months. The overall response rate to dapsone was 40%. Five patients responded in 1 month and one patient in 2 months. No pretreatment characteristics--sex, age, platelet count or duration of ITP--were correlated with response to dapsone. Treatment was well tolerated. The most frequent adverse effect was dose-related haemolytic anaemia. In our experience, dapsone provides an inexpensive and well-tolerated alternative for patients with ITP who had inadequate responses to conventional therapy.

Adolescent↗
PubMed1994

A case of the 'dapsone syndrome'.

The 'dapsone syndrome' developed in a 44-year-old woman who was treated for pyoderma gangrenosum with 100 mg/day dapsone for about 5 weeks. Symptoms included fever, malaise, jaundice with hepatic dysfunction, lymphadenopathy, mononucleosis and dermatitis. These symptoms disappeared with 30 mg/day of oral prednisolone. A lymphocyte stimulation test with dapsone was positive, as was the delayed-type intradermal skin test with 0.5 and 0.05% dapsone in saline. Immunohistochemical studies of the rash and skin test reaction revealed that the dominant infiltrating T cells in the upper dermis were of the Leu 2a+ cytotoxic/suppressor-type rather than the Leu 3a+ helper/delayed hypersensitivity-type.

Adult↗
PubMed1996

A comparative study of the efficacies of chloroquine and a pyrimethamine-dapsone combination in clearing Plasmodium falciparum parasitaemia in school children in Tanzania.

A randomized study on the in vivo efficacies of chloroquine and a pyrimethamine-dapsone combination (Maloprim) in clearing P. falciparum parasitaemia was carried out in 77 asymptomatic semi-immune schoolchildren in the Kilombero District of Tanzania. Children were randomized to receive either chloroquine at a dose of 25 mg/kg over three days, or Maloprim (6.25 mg pyrimethamine + 50 mg dapsone for children under 10 years, and 12.5 mg pyrimethamine + 100 mg dapsone for children 10 or more years old) as a single dose. Children were followed-up for malaria parasitaemia at days 2, 7 and 14 after screening, randomization and treatment. The slide positivity rate was lower in the Maloprim group at all cross-sectional surveys (23 vs 37% at day 2; 9 vs 20% at day 7; 21 vs 32% at day 14) but none of these differences reached statistical significance. No cases in the Maloprim group showed RII resistance, whereas in the chloroquine group, 2 cases showed RII resistance and a further 2 cases RIII resistance (6%). No major side-effects were reported. The combination of pyrimethamine-dapsone appears to be a better choice than chloroquine as a chemoprophylactic regimen for malaria in this area. Although they need to be confirmed in a larger study, these results may be of interest to the policy-makers as well as researchers.

Antimalarials↗
PubMed1957

Sulphadimidine, pyrimethamine and dapsone in the treatment of toxoplasmosis in mice.

Sulphadimidine, dapsone, and pyrimethamine have been tested alone and in various combinations for their therapeutic effect against toxoplasma infection in mice. In the treatment of active infection, sulphadimidine by itself was effective, but relapses were common. Pyrimethamine gave complete cures and prevented the carrier state when used in doses near to the toxic level. Dapsone alone was not as good as either of the other two drugs tested. The best combination was found to be sulphadimidine and pyrimethamine, which were synergic. In doses well below the toxic level, this combination not only controlled the acute infection but also prevented relapses and the development of the carrier state. Dapsone and pyrimethamine were also synergic, but were not as effective as the previous combination. No synergy was found between dapsone and sulphadimidine. The mechanism of relapse and the development of the carrier state and the modes of action of the drugs alone and in combination are discussed.

Animals↗
PubMed1979

Effects of gold, dapsone, and prednisone on serum C-reactive protein and haptoglobin and the erythrocyte sedimentation rate in rheumatoid arthritis.

Sequential measurements of serum C-reactive protein (CRP), serum haptoglobin (Hp), and erythrocyte sedimentation rate (ESR) were made in 209 patients with rheumatoid arthritis (RA); 78 of them were treated with gold, 71 with dapsone, and 60 with prednisone. The results were expressed as proportional changes in the measurements at 28-day intervals after treatment began. The period of study was 140 days. During treatment with gold and dapsone there were statistically significant gradual and progressive falls of similar magnitude in serum CRP and ESR. During treatment with prednisone serum CRP and ESR fell abruptly by 28 days and thereafter altered little. At 140 days prednisone had had the largest proportional effect on both measurements. During gold treatment the fall in serum Hp was similar to that of the ESR. In contrast, prednisone had little effect on Hp levels despite large falls in serum CRP and the ESR. Either prednisone stimulates Hp synthesis or the divergence is an expression of the difference in type of effect between gold and prednisone on RA. The effect of dapsone on serum Hp was large and progressive; it partly reflects haemolysis and, since the haemolysis was not progressive, partly improvement in the RA. The results show the relative efficacy of the drugs and suggest that dapsone may be a useful alternative treatment for RA.

Arthritis, Rheumatoid↗
PubMed1984

Report on chloroquine and dapsone in the treatment of rheumatoid arthritis: a 6-month comparative study.

A controlled study compared 6 months' treatment of 60 patients with rheumatoid arthritis (RA). Half were randomly allocated to treatment with chloroquine 250 mg daily, the other half dapsone 100 mg daily (50 mg/day for the first 7 days) following a one-month run-in assessment period. All patients had active or progressing disease. Both treatment groups showed significant improvement in morning stiffness, number of painful joints, pain scores, Ritchie index, and proximal interphalangeal joint size, and the chloroquine group alone in grip strength. Laboratory tests showed significant decreases in erythrocyte sedimentation rate, C-reactive protein, and total serum protein levels, with significant increase in serum albumin in the dapsone group, where there was a significant mean drop in haemoglobin (less than 1 g/dl) and a rise in serum bilirubin, associated with its haemolytic effect. X-ray erosion scores were not significantly affected. The clinical and laboratory responses became evident by the time of the 2-month assessment. Criteria for clinical and laboratory improvement were defined, according to which there were 21/26 improvers in the chloroquine group and 12/29 in the dapsone group. It is concluded that although both are effective preparations, chloroquine showed a significantly higher improvement rate and was certainly better tolerated. It is the preferred treatment for patients with active or progressive disease not controlled by nonsteroidal anti-inflammatory drugs, with dapsone as an alternative for patients who fail to respond to or cannot tolerate chloroquine.

Arthritis, Rheumatoid↗
PubMed1985

Reduction of neutrophil-mediated injury to pulmonary endothelial cells by dapsone.

The presence of activated neutrophils in the alveolar structures is thought to contribute to parenchymal cell injury in various acute and chronic lung disorders. This study indicates that dapsone (30 micrograms/ml), an agent with anti-inflammatory properties, can significantly reduce neutrophil-mediated injury to 51Cr-labeled bovine pulmonary artery endothelial (BPAE) cells with a reduction in the injury (expressed as a cytotoxic index) from 65 +/- 3 to 33 +/- 3 (p less than 0.001). Dapsone was unable to protect 51Cr-labeled BPAE cells injured by the chemical generation of superoxide, hydrogen peroxide, or neutrophil-derived, myeloperoxidase-dependent hypohalite ion. In contrast, dapsone significantly inhibited the respiratory burst of the neutrophil, with a reduction in the generation of superoxide, hydrogen peroxide, and conversion of nitroblue tetrazolium to formazan (p less than 0.01, all comparisons). Thus, dapsone appears to protect lung parenchymal cells such as endothelial cells from neutrophil-mediated injury by directly inhibiting the respiratory burst of the neutrophil, with a consequent diminution in the generation of toxic, oxygen-derived radicals.

Animals↗
PubMed1985

Investigation of the protective effects of the antioxidants ascorbate, cysteine, and dapsone on the phagocyte-mediated oxidative inactivation of human alpha-1-protease inhibitor in vitro.

Oxidants derived from the atmosphere or from activated pulmonary phagocytes mediate functional inactivation of alpha-1-protease inhibitor (alpha-1-PI). Chronic exposure to these oxidants may cause emphysema. In this study we have investigated the effects of the antioxidants ascorbate, cysteine (10(-4) M to 10(-1) M), and dapsone (10(-6) M to 10(-3) M) on the oxidative inactivation of human alpha-1-PI by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. During exposure of alpha-1-PI to stimulated PMNL in the presence of ascorbate and cysteine at concentrations of greater than 10(-4) M and dapsone at greater than 10(-6) M, the elastase inhibitory activity of alpha-1-PI was preserved. However, exposure of the alpha-1-PI to the antioxidants subsequent to PMNL-mediated oxidative inactivation was not associated with reactivation of elastase inhibitory capacity. Ascorbate, cysteine, and dapsone at concentrations that caused 50% protection of alpha-1-PI did not affect degranulation or the binding of radiolabeled leukoattractant to PMNL. It is suggested that the protective effects of the antioxidants are related to their ability to scavenge superoxide and oxidants generated by the PMNL-myeloperoxidase/H2O2/halide system. Because the effects of ascorbate and especially those of dapsone were observed at concentrations of these agents that are attainable in vivo, our results may have clinical significance.

Antioxidants↗
PubMed1978

The inhibition of polymorphonuclear leukocyte cytotoxicity by dapsone. A possible mechanism in the treatment of dermatitis herpetiformis.

The effect of the sulfone compound 4,4'-diaminodiphenyl sulfone (dapsone) on normal human polymorphonuclear leukocytes (PMNL) has been investigated in vitro. The drug has a dramatically beneficial effect in dermatitis herpetiformis in which the PMNL and immune complexes has been stressed to be of importance for the development of the skin lesions. Pruritus disappears and the inflammatory eruptions clear within a few days of starting therapy. The effect of dapsone has been evaluated on the different stages of phagocytosis. Using dapsone concentrations (1-30 mug/ml) comparable with those found after therapeutic doses, we have found that the drug interferes primarily with the myeloperoxidase (MPO)-H(2)O(2)-halide-mediated cytotoxic system in the PMNL. No effect was observed on random locomotion, chemotaxis, phagocytic ingestion, oxidative metabolism, or the release of lysosomal enzymes. Kinetic studies in a cell-free system with purified MPO revealed a competitive type of inhibition using varying concentrations of NaI. Furthermore, the inhibition resulted in reduced candidicidal activity during phagocytosis of Candida albicans, and reduced cytotoxicity to adjacent mammalian cells measured as the (51)Cr release from virus-induced lymphoma cells. Because the MPO-H(2)O(2)-halide system not only fulfills the antimicrobial activity but is suggested to be a modulator of the inflammatory reaction as well, the action of dapsone in dermatitis herpetiformis may in part be explained by its effect on this system.

Adolescent↗
PubMed1996

Combined dapsone and clofazimine intoxication.

We report clinical findings and pharmacokinetic data regarding a combined dapsone and clofazimine intoxication in a man, who ingested 50 tablets of dapsone (100 mg) 20 capsules of clofazimine (100 mg) and two tablets of rifampicin (600 mg). Oral administration of activated charcoal (50 grams) and sodium sulphate (20 grams) after gastric lavage resulted in an elimination half-life in plasma of 11.1 and 10.8 h for dapsone and its main metabolite, monoacetyldapsone, respectively. A rapid initial decrease of the plasma concentration of clofazimine was observed after gastric lavage and administration of activated charcoal and sodium sulphate. 15 h after this treatment, clofazimine plasma levels remained relatively constant. Dapsone-induced methaemoglobinaemia (48% at admission) was treated successfully with methylene blue.

Adult↗
PubMed2005

Dapsone syndrome with acute renal failure during leprosy treatment: case report.

Dapsone syndrome is a rare hypersensitivity reaction to dapsone and is characterized by high fever, papular or exfoliative dermatitis, progressing to liver toxicity and generalized lymphadenopathy, resembling a mononucleosis infection. We report a patient who developed acute renal failure, as well as other complications characteristic of dapsone syndrome, during leprosy treatment. Renal involvement had not been previously described as a dapsone syndrome feature.

Acute Kidney Injury↗
PubMed1995

Dapsone-induced hemolytic anemia.

Dapsone, an old drug introduced and used almost exclusively for the treatment of leprosy, is now utilized in an increasing number of therapeutic situations. However, its hemotoxicity is potentially severe and is often dose limiting. Effective countermeasures, based on resolution of the mechanisms underlying dapsone-induced hemotoxicity, could significantly enhance the therapeutic value of the drug. In studies on rat red cells, we have established that the N-hydroxy metabolites of dapsone, DDS-NOH and MADDS-NOH, are direct-acting hemolytic agents, that they are formed in amounts sufficient to account for the hemotoxicity of the parent drug, and that the action of these toxic metabolites in the red cell induces premature sequestration by the spleen. Incubation of rat red cells with hemolytic concentrations of arylhydroxylamines leads to the generation of hydroxyl, glutathiyl, and hemoglobinthiyl radicals, and the formation of protein-glutathione mixed disulfides. Disulfide-linked adducts are also formed between membrane skeletal proteins and hemoglobin monomers, as well as between the monomeric hemoglobin units forming dimers, trimers, tetramers, and pentamers. Profound morphological changes are seen with change from normal discoidocity to an extreme nonspherocytic enchinocyte shape. Parallel studies with human red cells indicate that the response of human cells is qualitatively similar but that there are notable differences in regard to skeletal membrane effects. A working hypothesis for the mechanism underlying dapsone hemolytic activity is proposed.

Anemia, Hemolytic↗
PubMed1977

Agranulocytosis due to dapsone.

A case of agranulocytosis due to dapsone administered for the treatment of acne vulgaris is described. Agranulocytosis has previously been reported after administration of dapsone for other dermatological disorders, leprosy, and prophylaxis against falciparum malaria. The frequency of agranulocytoses when dapsone was used for malaria prophylaxis in United States servicemen in Vietnam was sufficient to result in its withdrawal from use for this purpose. Caution should therefore be exercised in the administration of dapsone for conditions for which less toxic agents are available.

Adult↗
PubMed1990

Evaluation of five treatment regimens, using either dapsone monotherapy or several doses of rifampicin in the treatment of paucibacillary leprosy.

The objective of the present study was to define short-course treatment regimens for PB leprosy and to compare them with the 'classical' dapsone treatment and the WHO-PB regimen. Five treatment regimens were studied and evaluated by the histologic evolution. The regimens were: (1) dapsone 100 mg daily, non-supervised for 3 years; (2) RMP 900 mg supervised, once weekly, 8 doses; (3) idem 12 doses; (4) RMP 600 mg, once monthly, supervised, 6 doses and during this treatment dapsone 100 mg daily unsupervised; (5) RMP 600 mg together with dapsone 100 mg daily, supervised for 6 days. For each of these regimens there were between 114 and 195 person-years of follow-up. Results are comparable for the 5 treatment regimens, and reach 65-75% cure rates at 36 months and 80-90% at 48 months after the start of therapy. The relapse rate for all groups is about 0.5% per year. The difficulty for the diagnosis of relapse in PB leprosy is discussed. It is concluded that treatment of PB leprosy can be relatively simple but that a relatively long time is needed to evaluate its effect.

Dapsone↗
PubMed1997

Influence of acetylator phenotype on the haematological and biochemical effects associated with dapsone in leprosy patients.

Methaemoglobinaemia and haemolytic anaemia were the principal side-effects observed in 30 leprosy patients undergoing long-term treatment with dapsone as a single drug or as part of multidrug therapy. Hepatic, pancreatic and renal evaluations showed no relevant clinical changes. Since N-acetylation is a major metabolic pathway for dapsone, slow acetylation phenotype may be a risk factor for the development of these reactions. To confirm this hypothesis we correlated acetylator phenotype and the haematological and biochemical effects induced by dapsone. No excess proportion of slow acetylators was found. We conclude that slow acetylators are not at greater risk of developing haematological side-effects of dapsone than fast acetylators.

Blood Cell Count↗
PubMed1981

Fatal reaction to dapsone during treatment of leprosy.

A Burmese boy being treated with dapsone (diaminodiphenylsulfone [DDS]), 100 mg daily, for lepromatous leprosy had a fatal reaction to the drug 3 weeks after therapy was started. The clinical symptoms and progression of illness conform well to a "DDS syndrome" first described in the early 1950s. Although the syndrome clinically resembles infectious mononucleosis, neither Epstein-Barr virus nor cytomegalovirus was implicated as an etiologic agent in this case. The syndrome has been recognized during initiation of dapsone therapy for lepromatous leprosy and has led to the use of a prolonged induction period with initial dosages as low as 25 mg/week. However, because dapsone resistance has been recognized in some strains of Mycobacterium leprae, slow induction of therapy has been replaced with the schedule used for this patient. This report of a fatal reaction to dapsone emphasizes the need for caution when initiating therapy with the drug at full dosage.

Adolescent↗
PubMedDate not supplied

Simultaneous determination of dapsone and pyrimethamine by derivative spectrophotometry in pharmaceutical formulations.

A simple and fast method was developed for the simultaneous determination of dapsone and pyrimethamine by first-order digital derivative spectrophotometry. Acetonitrile was used as a solvent to extract the drugs from the pharmaceutical formulations, and the samples were subsequently evaluated directly by digital derivative spectrophotometry. The simultaneous determination of both drugs was performed by the zero-crossing method at 249.4 and 231.4 nm for dapsone and pyrimethamine, respectively. The best signal-to-noise ratio was obtained when the first derivative of the spectrum was used. The linear range of determination for the drugs was from 6.6 x 10(-7) to 2.0 x 10(-4) and from 2.5 x 10(-6) to 2.0 x 10(-4) mol/L for dapsone and pyrimethamine, respectively. The excipients of commercial pharmaceutical formulations did not interfere in the analysis. Chemical and spectral variables were optimized for determination of both analytes. A good level of repeatability, 0.6 and 1.7% for dapsone and pyrimethamine, respectively, was observed. The proposed method was applied for the simultaneous determination of both drugs in pharmaceutical formulations.

Antimalarials↗